TY - JOUR
T1 - MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease
T2 - A double-blind, randomized, placebo-controlled clinical trial
AU - Luisetti, M.
AU - Sturani, C.
AU - Sella, D.
AU - Madonini, E.
AU - Galavotti, V.
AU - Bruno, G.
AU - Peona, V.
AU - Kucich, U.
AU - Dagnino, G.
AU - Rosenbloom, J.
AU - Starcher, B.
AU - Grassi, C.
PY - 1996
Y1 - 1996
N2 - We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/posttreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.
AB - We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/posttreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.
KW - chronic bronchitis
KW - elastin
KW - plasma elastin-derived peptides
KW - pulmonary emphysema
KW - urinary desmosine
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U2 - 10.1183/09031936.96.09071482
DO - 10.1183/09031936.96.09071482
M3 - Article
C2 - 8836663
AN - SCOPUS:8944254696
VL - 9
SP - 1482
EP - 1486
JO - European Journal of Respiratory Diseases
JF - European Journal of Respiratory Diseases
SN - 0903-1936
IS - 7
ER -